The objective of this proposed research is to develop stereospecific methods for the synthesis of the new and diverse sterol side chains that have recently been found in mammalian, plant, insect, marine, and fungal sterols. Our proposed synthetic route will provide analogs of withaferin A, a useful antitumor agent in the mouse, and analogs of previtamin D3, which may possess vitamin D3 agonist or antagonist activity. Synthetic sterol analogs will be tested as well for antibiotic and other metabolic activities. A rapidly expanding number of sterol side-chain structures are being uncovered in nature that are functionalized variations on the prototype cholesterol side chain. The research proposed herein is designed to develop new side-chain synthetic methodology that will provide preparatively useful routes to many of these new sterols. Our synthetic studies will aid in the isolation and identification of these sterols with new side-chain structures and will facilitate their biochemical studies. An important feature of our synthetic approach is the complete stereochemical control that we are able to maintain at the important C-17 and C-10 centers of the sterols in placing the side chain onto readily accessible pregnanes and androstanes. In general, the proposed synthetic strategy permits the highly stereocontrolled attachment of an acyclic side chain onto a ring system.